Influenza H1N1: Between the Laboratories and the Health Authorities. are there Dangerous Liaisons?

Excessive orders for vaccines, doubts concerning their safety, failure to guarantee independence of experts, low rates of vaccination ... The calamitous management of the influenza H1N1 has created a rise in defiance with respect to public powers. These suspicions were nourished by previous errors involving contaminated blood transfusions and public health procedures during the summer heat wave. At the heart of these polemics, the links and possible conflict of interest between health officials and pharmaceutical laboratories.

After the emotion, commissions of inquiry now multiply, to clarify the situation. First to put their foot in the plate, the Council of Europe, under the leadership of Wolfgang Wodarg German member of parliament. On 27 January this year started the first hearings of the Health Commission on the realities of the epidemic [1]. In France, the new centrist group Nouveau Centre in the National Assembly issued a demand for a commission similar to that which should be set up next February 24 [2]. In the Senate, at the demand of the Communist senators and those of the Party of the Left, a commission "on the role of pharmaceutical firms in the management by the Government of the influenza A" was decided yesterday. The designation of the members of this commission will be voted in the session of Wednesday 17 February. While waiting for these first reports and analyses, l’Humanité places face to face the president of the pharmaceutical industry owners group (the Leem), Christian Lajoux, and the senator and doctor François Autain, who originated the call for this Senate inquiry.

Huma:Mister Autain, in the name of the group of Communist and Republican Senators and from the Party of the Left, you have asked for the creation of a commission of inquiry to determine the role played by the pharmaceutical companies in, and I quote you, "the management of a fantasy epidemic". What is the basis for this action?

François Autain: When the WHO [World Health Organization] decreed its maximum alert, level 6, in June 2006, we were already in possession of certain elements that tended to prove that this influenza was no worse than a seasonal flu, elements furnished in particular by the Centers for Disease Control, a United States agency for public health, the equivalent of our Institut de veille sanitaire [Institute for Public Health Surveillance]. The WHO did not take these indications into account. This is surprising. Given the time, we were able to learn from what happened in the southern hemisphere, and what we observed, in fact, was in no way comparable with what we had feared. But, from the moment that the WHO set off its alert of a pandemic, the French government zealously put its recommendations into effect. And I still pose myself this question: why did we order so many doses of the vaccine? Especially since, as indicated by the High Council on Public Health, a vaccination against the influenza H1N1 had no chance of controlling the process except in the case that it had commenced less than a month after the virus had begun to contaminate the population. We could have well known, when ordering the vaccines, that they would not be available before the month of November. There was consternation, that I can understand, but the principle of due precaution should not erase the principle of evaluation : we had at that time scientific measurements that permitted us to relativize the danger.

Christian Lajoux: For a period of months we were faced with incertainties, with scientific unknowns. The WHO had made its announcements. It’s too easy to tell a story after the fact! What were they asking of us, of the pharmaceutical laboratories? In the face of a pandemic, with a new virus, for which we had no measure of all its possible effects, they asked us to make ready a vaccine as quickly as possible. The development of a new sample of vaccine requires an incompressible delay of at least five months. The industry then made this clear to the health authorities. At that point, we were still confronted by unknowns concerning the gravity of the pandemic, on the dosage of the antigen, and on the number of injections. The health authorities did not opt for a single injection until November. But the machinery was already up and running, and [this rapid startup] had completely upset research plans and the implementation of industrial fabrication in those companies involved in production of the vaccine.

François Autain: I have no argument with this presentation of the situation in which the laboratories found themselves when the alert was given and the orders for vaccines issued. My criticism concerns the alert itself, the definition of a pandemic. We can’t react in the same way to a virus that propagates very rapidly, but is not serious : we can’t compare the H1N1, for which the mortality rate is 1 in 100,000, to H5N1, which is very virulent, with a 30% mortality rate.

Christian Lajoux: We didn’t know this at that time.

François Autain In June, however, we had the epidemiological elements permitting us to say "this is not the H5N1". I’m ready to admit that there were incertitudes, but there was no basis in fact to declare a maximum pandemic alert.

Christian Lajoux: There were many unknowns. In the end we concluded that the pandemic was less strong, but I would still be careful today not to say that we know everything about the future of this virus, nor to say that the danger is passed. As for me, what I fear is that vaccination will be the real loser. We are putting so much emotion in to the debate. We observed, in this episode, how the anti-vaccine movement was strongly reanimated, and there are risks of increased fragility in terms of prevention.

François Autain: Mister Lajoux, you also have been the victim of a tendency toward dramatization. One loses sight of objective reality, of the facts, of epidemiological inquiries, in order to launch into cataclysmic predictions for which we already possess the proof that they have no correspondence with reality. Dramatization was consistently a leading element in this affair, and the risk was constantly overestimated. This is a fundamental problem.

Christian Lajoux: Of course, we asked ourselves questions about the intensity of the pandemic, about the best type of vaccine to produce, and the number of injections. But at no point was the issue of the debate decided, and I’m nevertheless inclined to believe the national public health authorities of this country. I think it’s necessary to clarify things in the wake of this episode. We should have, on all sides, politicians, industrialists, health authorities, some humility with respect to what has transpired, the errors that may have been made, and what lessons we can draw from this. Questions are posed, and as a pharmaceutical industrialist, I stand ready to serve. But this must develop through dialog, debate, and objectification. Not through feeding old fears of industrial "conspiracy" behind the pandemic. That just doesn’t hold up!

François Autain: I agree to recognize that, alas, this crisis has multiplied the number of adversaries to vaccination-as-such. We should study the reasons for this. The moment one launches into a vaccination campaign that seems unjustified to a majority of citizens, we can understand why a certain number of them will ask themselves whether what we ask of them at other moments is not equally useless.

Was the credibility of vaccination not also damaged by interrogations concerning the use of additives in the fabrication of vaccines, additives for which safety had not been proven? Mister Lajoux, didn’t the laboratories deliberately take risks there?

Christian Lajoux: The reply is clearly "no". The medical industry has an ethic of research and fabrication. The development of the vaccine against the virus H1N1 proceeded exactly as it has for any other vaccine. The time period was the same, the use of additives has been known for decades, they are well documented, and they pose no danger to the population.

François Autain: You say that additives were already used, forgetting to make clear that this was for persons of over 75 years of age. There has been no testing at all for children ...

Christian Lajoux: In saying that, you are fueling the anti-vaccination movements that cast a priori suspicion, on unscientific grounds,
on an act of preventative medicine. We have a shared responsibility. Let’s make sure that vaccination doesn’t become the loser.

François Autain: Well, then, we should market vaccines that won’t be the subject of controversy!

Christian Lajoux I often hear it said, "the laboratories did this, they did that." The laboratories are under the permanent control by health authorities, national and European. They don’t decide all alone the indications for a drug, the precautions to be observed in its use, the manner of administration, the vaccines they will develop, what research they will do, or what they will produce. It is always, and so much for the better, the health authorities who decide.

François Autain: The laboratories have, however, means with which to influence the decisions of the health authorities.

Christian Lajoux: That’s the "big conspiracy" theory.

François Autain: It is eminently clear that a large number
of tests are falsified in order to make it appear that a medication is more reliable and effective than it is in reality. There was the affair Vioxx, the affair Deroxat... Presently, for vaccines as for any other medication, the tests are financed exclusively by the pharmaceutical industry. Once these tests are carried out, it is the commission AMM [3], that authorizes the launching of drugs on the market. The AMM,
part of the Afssaps [4], decides whether the medication will be authorized or not. The Afssaps, in order to carry out its analysis, is obliged to consult experts with interests linked to the pharmaceutical industry. All the experts who make up the AMM commission have links to the industry. There is a suspicion as to the independence of the decisions rendered by this commission. And we must add that it is you, the industry, that finances the Afssaps.

Christian Lajoux: Falsification of research? That’s disinformation. In the scientific world, there is a permanent evolution in knowledge and a constant questioning of apparent certainties. So, there has indeed been a revision of a certain number of files. And sometimes, medications are withdrawn from the market, about two or three each year, which is very few. This isn’t a question of deceitfulness, or of falsification in the planning of clinical studies. The industry finances the studies? Yes, but this is under the constant control of health authorities, who, at each stage in the development of the medication, give their opinion as to whether development should continue or not. It is an insult to the authorities of our country to let it be suggested that they would accept transgressions of ethical or deontological rules. That would be to cast suspicion on the 100,000 collaborators who work in the medicinal industry, in France, who have the sentiment that they take their work seriously, and that they aim for quality.

François Autain: I am not casting suspicion on your collaborators, but on the capacity, the will, of health autorities to control the tests. They do not have the means. You are completely free. For the tests, in the case of the anti-influenza vaccinations, this is what the High Council for Public Health said in June 2009: "It appears likely that these vaccines will be made available despite the fact that, with respect to immuno-genicity and tolerance, they will not have been evaluated for certain age brackets. ... The determination of those populations that can be targeted for an obligatory vaccination will be difficult to make, and may change with time. Finally, the evaluation of these vaccines with respect to tolerance will be necessarily minimal at the point at which their utilization will be decided." Which means that we marketed vaccines that had been inadequately tested.

Christian Lajoux: Every time there is a debate on health issues, it’s the same story: some people have a vested interest in stigmatizing the pharmaceutical industry, and a desire to scare the citizens about a certain number of things. Let’s look seriously at this. We can’t let these suspicions weigh on the health authorities in our country, and we can’t let it be thought that the pharmaceutical industry finances the Afssaps, while the fact is that the industry is taxed, and the proceeds of this tax contributes to financing the Afssaps. We can’t let it be thought that the idustrialists develop medicines all on their own.

François Autain:
The episode of the influenza H1N1 has nevertheless put the spotlight on the question of independence, relative to the laboratories, of the experts who counsel the public health authorities ...

Christian Lajoux: Today there is a law that obliges scientific experts and medical people working for parmaceutical companies to make a declaration, and the authorities have the obligation to publish these links. When you visit the web site of the Afssaps, you see these links. This means that if I work with such and such laboratory I am not eligible to evaluate a product by that same laboratory, just as I can not evaluate a competing product. Perhaps we should be working for more transparency. I call, in the name of the industrialists, for complete transparency. It must also be the case that, when health professionals speak, they explain for whom they speak: "I am such-and-such doctor or health professional, I have just completed a publication about such-and-such medication, and I state to you that I am working for such-and-such company."
We will never reach a state where we have enough experts who don’t work for industry and can, moreover, give an opinion. But in any case, as an industrialist, I am ready to work on this.

François Autain: To speak about experts, we must localize the considerable importance that the pharmaceutical industry has in our society. I don’t reproach you for your work, but I deplore the fact that, in front of you, there is nobody. You intervene even in the early training of students, and in the continuing education of doctors. When a medication has been placed on the market, you organize enormous means in order to make publicity to doctors. A report by the Igas estimated 25,000€ per year, per doctor, in expenses for publicity. As for experts, the problem is differently posed when the health authorities are reinforced, when they have acquired greater independence concerning their financing, and when they have an expertise internal to their offices, which, today, does not exist. What the Afssaps receives from the state doesn’t even finance their missions. As for transparence, it is necessary but not sufficient: it’s not because an expert has declared that he has financial links with many laboratories that he will be free of all dependence. We must dissociate the experts who counsel and work with the laboratories from those who are to be found in the health authorities, who are there to determine the appropriateness of marketing or not a given medicine. Today there exists a confusion of roles, very damaging to independence and reliability of decisions taken. To avoid imputing motives, it must really not be the case that the same experts be involved in these two roles. Once that is true, the question of transparency will lose some of its importance.
Today, few experts are sanctioned, they are not required to declare everything, they risk nothing. Only an independent authority charged with overseeing the establishment of this statute will permit us to remedy these gaps. Are the laboratories ready to accept more public control of their activities?

Christian Lajoux: Matters have moved a lot in recent years, and we are moving in the direction of more transparency. We are conscious that we cannot have any confusion of roles. I think nevertheless that today there are not, or at least not many, situations of potential conflict of interest. Persons designated to give expert opinions declare their positions. But there is always room for improvement. I am not hostile to the
supervision of industrial activities and to control, especially when it comes to health, quality and health monitoring. I tend to trust in the authorities of our country.

François Autain:
The pharmaceutical industries are not like other industries: they do not address themselves directly to the consumers, their prices are not free but administered, and they benefit for public financing. It is thus normal that their activities be controlled. The accounting of these enterprises should be entirely public and open to all.

Tests should not be financed by laboratories, but by independent authorities, in order to eliminate all suspicion. We should not put on the market medicines that do not afford any proven new utility.

Interview organized by Lionel Decottignies and Yves Housson

[1] A pandemic (from Greek πᾶν pan "all" + δῆμος demos "people") is an epidemic of infectious disease that is spreading through human populations across a large region; for instance a continent, or even worldwide.

[2] This article was published in l’Humanite of 12 February 2010. We publish the translation, now available, because of the continuing relevance of the issue.

[4] Afssaps : Agence française de sécurité sanitaire des produits de santé, the French agency for sanitary security in health-related products. This is a public agency placed under the control of the minister of health. Its purpose: to assure safety in the use of health products for people. Its mission: to evaluate and inform in matters of benefits and risks, to control quality, inspect and watch over fabrication sites, distribution, and testing.